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Cl-Necrostatin-1 is an inhibitor of receptor-interacting protein kinase 1 (RIPK1).1 It inhibits RIPK1 activity when used at concentrations of 0.3, 3, and 30 µM. It also inhibits TNF-α-induced necroptosis in Jurkat cells deficient in Fas-associated death domain protein (FADD; EC50 = 180 nM), a modification that prevents caspase activation in response to death-domain receptor signaling.2,3 Cl-Necrostatin-1 (2 µl of a 4 mM solution, i.c.v.) reduces infarct size when administered pre- and post-occlusion, or post-occlusion only, in a mouse model of middle cerebral artery occlusion (MCAO).
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1. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat. Chem. Biol. 4(5), 313-321 (2008).
2. Structure-
3. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat. Chem. Biol. 1(2), 112-119 (2005).